The Role Of DNA Sensing In The Pathogenesis Of Colorectal Cancer
Funder
National Health and Medical Research Council
Funding Amount
$633,704.00
Summary
Colorectal (bowel) cancer is a leading cause of death in Australia and worldwide. The ability of the body to detect DNA from damaged or dying cells in the gut is an important part of the healing process. This response also provides protection against colorectal cancer. In this project, we investigate how a DNA sensor prevents the development of intestinal tumours. This project will lead to new ways to fight cancer in humans.
Defining Biomarkers Of Colorectal Cancer Prevention By Dietary Agents And Translation To Human Intervention Studies
Funder
National Health and Medical Research Council
Funding Amount
$632,924.00
Summary
This research will explore dietary agents for their ability to regulate the damage to DNA that is responsible for causing bowel cancer. The plan is to identify a dietary approach that will effectively reduce the risk of colon cancer. The science will be tested in animal models followed by initial human experiments aimed at testing the relevance to humans.
Role Of MACROD2 Loss In DNA Repair, Chromosomal Instability And Development Of Colorectal Cancer: Clinical And Therapeutic Implications
Funder
National Health and Medical Research Council
Funding Amount
$772,871.00
Summary
The MACROD2 gene is deleted in one-third of human bowel cancers. We have discovered that MACROD2 deletion causes defective DNA repair and tumour chromosomal instability. Here, we will use novel laboratory models to show that MACROD2 loss actively promotes bowel cancer development. We will test the clinical implication of MACROD2 loss for predicting tumour therapy response and will investigate the potential of exploiting this deficiency for drug targeting.
Molecular And Therapeutic Interactions In Colorectal Cancer
Funder
National Health and Medical Research Council
Funding Amount
$670,409.00
Summary
This project will use our unique preclinical models to unravel the molecular and cellular events underlying the cooperation between two important cancer-causing pathways, PI3K and Apc/Wnt, in driving the development of cancer in the gastrointestinal tract. Our studies will provide critical new insights into the clinical significance of this interaction as well as the potential role of these pathways in the prophylactic and therapeutic actions of aspirin in the context of colorectal cancer.
Elucidating The Role Of Claudin-2 In Tumour Initiation And Metastasis Development From Colorectal Cancer: Consequence For Tumour Relapse
Funder
National Health and Medical Research Council
Funding Amount
$398,993.00
Summary
Mortality from colorectal cancer is often due to the development of metastases. Cancer stem cells (CSC) are suspected to provide a major drive for metastasis development, to resist current therapies, and to initiate tumour relapse. Yet, little is known about mechanisms that control CSC behaviour. Our project investigates the role of claudin-2, a cell adhesion protein that is strongly overexpressed in colorectal cancer, in the regulation of CSCs, metastasis development and tumour relapse.
Functional Studies On The Role Of DNp73 In Stem Cells And Cancer
Funder
National Health and Medical Research Council
Funding Amount
$428,838.00
Summary
This project investigates the role of the p73 gene in regulating stem cells and facilitating intestinal cancer formation. We hypothesize that when a particular form of this gene (DNp73) is upregulated it prevents differentiation of stem cells and promotes tumour formation. We combine novel approaches in mice and fruit flies to examine the function of DNp73 in stem cells with analysis of human tumour samples. These studies may identify a new target for tumour therapy.
The Nature And Significance Of Clonal Evolution In Human Melanoma
Funder
National Health and Medical Research Council
Funding Amount
$665,420.00
Summary
Cancers can progress in patients by developing genetic changes that favor the growth, survival and spread of cancer cells. However, the rate at which genetic changes occur in human cancer is not known. This project will determine the degree and biological significance of genetic change in human melanoma by using a novel method of growing tumors from single cells and comparing genetic differences between them.
Investigating Signalling Pathways That Mediate Suppression Of Anoikis By Chemokine Receptors In Metastatic Breast Cancer Cells
Funder
National Health and Medical Research Council
Funding Amount
$597,349.00
Summary
This research aims at understanding the "nuts and bolts" of the main killer in cancer patients - tumour metastasis. We will look for molecules that are specific to metastatic tumour cells that transmit signals from the cell surface to the cell "suicide" machinery and prevent metastatic cancer cell death.
Effects Of A Novel Hotspot Mutation Of Brm In Non-Melanoma Skin Cancer Development
Funder
National Health and Medical Research Council
Funding Amount
$92,314.00
Summary
Australia has the highest incidence of skin cancer in the world. SWI/SNF, a yeast nucleosome remodeling complex, is known destabilise interactions in DNA. It is made up of 8-10 proteins, including a novel tumour suppressor Brm. There is some evidence that Brm acts as a tumour suppressor in skin cancer, but relevance of a recently found mutation in Brm is yet to be characterised. This project aims to identify the effect of this mutation, on cellular sensitivity to UV radiation and examine transfo ....Australia has the highest incidence of skin cancer in the world. SWI/SNF, a yeast nucleosome remodeling complex, is known destabilise interactions in DNA. It is made up of 8-10 proteins, including a novel tumour suppressor Brm. There is some evidence that Brm acts as a tumour suppressor in skin cancer, but relevance of a recently found mutation in Brm is yet to be characterised. This project aims to identify the effect of this mutation, on cellular sensitivity to UV radiation and examine transformation to malignancy.Read moreRead less